It is well known that fetal alcohol syndrome children are particularly susceptible to infections during early childhood, and the mechanisms by which immunological competence is transmitted from mother to infant and the development of the babies' own immune system represent important interest areas for the expression of immunity during the neonatal period. The widespread use of medications and the abusive use of ethanol and other drugs have lead to concern for the welfare of breast-fed infants from all sectors of society. For lactational immunity, potential mechanisms for detrimental effects of ethanol include changes in the capacity of the maternal immune system to generate immune components, structural or functional alterations in the mammary gland that affect delivery of immune components to the baby, and the effects of ethanol present in utero and in milk on the development of the neonate's immune system. Using established techniques in our laboratory, continuing assessments will be made as to the effects that maternal and neonatal alcohol consumption have on: 1) the transfer of immune factors to the neonate during lactation and immune expression in the baby using two model systems, T.spiralis parasitic infection and contact sensitization to TNCB; 2) the leukocyte content in mammary tissue and milk and the expression of Class I and II MHC antigens, especially during T.spiralis or TNCB sensitivity; 3) the development of the neonatal gastrointestinal immune system; 4) long-term longitudinal studies on the passage of lactational immunity to the second generation of babies born to FAS affected mothers; and 5) methods to reverse the deleterious effects of maternal or neonatal alcohol consumption by altering the nutritional status through protein content of the diet, adoptively administering normal or sensitized immune cells or administering immunostimulatory agents to the alcoholic mother or neonate. In addition, the effects of combined drug abuse (alcohol and marijuana) on placental and lactational transfer of immunity will be assessed. An understanding of the effects of maternal alcohol consumption on the passage of immunity during suckling and the consequences of neonatal alcoholism to the development of the baby's own immune system may help to explain the increased risk infants have to diseases during the neonatal period. In addition, since an increasing number of women are drug abusers and also abuse alcohol, this research has significant implications in the well-being of infants born to women in the high-risk population for AIDS.